神经系统疾病中 GABA A 受体的功能调节。
Functional regulation of GABAA receptors in nervous system pathologies.
机构信息
Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA.
出版信息
Curr Opin Neurobiol. 2012 Jun;22(3):552-8. doi: 10.1016/j.conb.2011.10.007. Epub 2011 Oct 28.
Abstract
Inhibitory neurotransmission is primarily governed by γ-aminobutyric acid (GABA) type A receptors (GABAARs). GABAARs are heteropentameric ligand-gated channels formed by the combination of 19 possible subunits. GABAAR subunits are subject to multiple types of regulation, impacting the localization, properties, and function of assembled receptors. GABAARs mediate both phasic (synaptic) and tonic (extrasynaptic) inhibition. While the regulatory mechanisms governing synaptic receptors have begun to be defined, little is known about the regulation of extrasynaptic receptors. We examine the contributions of GABAARs to the pathogenesis of neurodevelopmental disorders, schizophrenia, depression, epilepsy, and stroke, with particular focus on extrasynaptic GABAARs. We suggest that extrasynaptic GABAARs are attractive targets for the treatment of these disorders, and that research should be focused on delineating the mechanisms that regulate extrasynaptic GABAARs, promoting new therapeutic approaches.
摘要
抑制性神经传递主要由 γ-氨基丁酸 (GABA) A 型受体 (GABAARs) 控制。GABAARs 是由 19 种可能的亚基组合形成的异五聚体配体门控通道。GABAAR 亚基受到多种类型的调节，影响组装受体的定位、性质和功能。GABAARs 介导突触（突触）和紧张（突触外）抑制。虽然调节突触受体的调控机制已经开始确定，但对突触外受体的调节知之甚少。我们研究了 GABAARs 在神经发育障碍、精神分裂症、抑郁症、癫痫和中风发病机制中的作用，特别关注突触外 GABAARs。我们认为，突触外 GABAARs 是这些疾病治疗的有吸引力的靶点，应该集中研究调节突触外 GABAARs 的机制，以促进新的治疗方法。
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